This invention relates to the treatment of colic and teething, two conditions that afflict a significant portion of babies and young children.
Colic is a symptom complex characterized by paroxysms of presumably severe abdominal pain and crying with irritability and fussing in an otherwise healthy infant. These episodes usually occur during the first one and one-half to nine months of life and afflict up to 40% of infants. There are a number of known and presumed causes of this condition including milk allergy, under feeding, over feeding, high carbohydrate diet, ineffective burping, excessively large holes in the nipple, excess air sucked in, changes in handling, feeding, and sleeping routines, stimulus overload, anxious parents, and gastrointestinal smooth muscle cramping. To be effective, therapeutic drugs must do more than merely relieve pain, since pain plays a minor role if any in colic.
Teething is another symptom complex occurring in nearly all infants and toddlers to some degree at three to eighteen months of age. Teething is characterized by pain, tenderness, edema, excess salivation, irritability and insomnia. These symptoms result from migration and eventual eruption of deciduous teeth through the oral mucosa.
Current therapies for colic are generally discouraging, especially for severe episodes. On a short-term basis, mechanical maneuvers such as rhythmic motions are often beneficial. Pharmaceutical intervention, however, should be reserved for prolonged episodes, i.e., those exceeding three weeks. Attempts with the latter have included sedation with either antihistamines or phenobarbital, a long-acting barbiturate. Unfortunately, these have met with limited success. Phenobarbital is particularly undesirable since it usually produces excessive irritability when the sedation subsides.
Another seemingly likely candidate would be dicyclomine, a tertiary amine with antimuscarinic activity that has a published efficacy of 63%. Unfortunately, dicyclomine is limited by a narrow margin of safety due to its known induction of apnea, seizures, and coma. As a result, it is absolutely contraindicated in babies less than six months of age.
In the case of teething, known therapies include providing firm, blunt or cool objects for the baby to bite on, and very short-acting topical anesthetics. There are no other treatment regimens except sedation.
Two combinations of an antihistamine with a barbiturate have been used in the treatment of teething and colic and have demonstrated efficacy for both conditions.
The first is the combination of diphenhydramine (2-diphenylmethoxy-N,N-dimethylethanamine hydrochloride; available from Parke Davis & Co., Morris Plains, N.J., as Benadryl Elixir) and butabarbital sodium (5-ethyl-5-(1-methylpropyl)-2,4,6(1H,3H,5H)-pyrimidinetrione sodium salt; available from Wallace Laboratories, Cranbury, N.J., in both powder form and as Butisol Elixir). The combination has been formulated by mixing 650 mg butabarbital sodium powder in enough water to form a paste, then combining the paste with 120 mL of Benadryl Elixir which contains 12.5 mg diphenhydramine per 5 mL including 14% ethanol, and finally adding 3 drops of hydrochloric acid to clear the solution. The dosage is 1/2-1 teaspoonful diluted in 1/2-ounce milk or juice administered orally at the onset of symptoms and repeated every 4-8 hours as needed.
The second combination is that of promethazine hydrochloride (N,N,.alpha.-trimethyl-10H-phenothiazine-10-ethanamine; available from Wyeth Laboratories, Philadelphia, Pa., as Phenergan syrup) and butabarbital sodium. This combination has been formulated by mixing equal parts of Butisol Elixir (which contains 30 mg butabarbital sodium per 5 mL including 7% ethanol) and Phenergan syrup (which contains 6.25 mg promethazine hydrochloride per 5 mL including 7% ethanol). The dosage is 1-2 teaspoonsful administered orally at the onset of symptoms and repeated every 4-8 hours as needed.
These two combinations have been administered by the inventors herein as therapy to patients in a pediatrician's office in Ontario, Oreg., as part of their practice in pediatrics over a period of fifteen years prior to the filing date of the present application.